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Record W4401246274 · doi:10.1038/s41467-024-50849-1

Transcriptional regulation of the postnatal cardiac conduction system heterogeneity

2024· article· en· W4401246274 on OpenAlexafffund
Yena Oh, Rimshah Abid, Saif Dababneh, Marwan Bakr, Termeh Aslani, David P. Cook, Barbara C. Vanderhyden, Jin G. Park, Nikhil Munshi, Chi‐chung Hui, Kyoung-Han Kim

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsUniversity of TorontoOttawa HospitalUniversity of British ColumbiaHospital for Sick ChildrenUniversity of Ottawa
FundersCanadian Institutes of Health ResearchKyungpook National UniversityGovernment of CanadaNatural Sciences and Engineering Research Council of CanadaOttawa Hospital Research InstituteUniversities Space Research AssociationGovernment of OntarioNational Heart, Lung, and Blood InstituteHeart and Stroke Foundation of CanadaHospital for Sick ChildrenUniversity of Ottawa Heart Institute FoundationUniversity of Ottawa
KeywordsGene regulatory networkSinoatrial nodeTranscriptomeBiologyElectrical conduction system of the heartAtrioventricular nodeBundle branchesRegulation of gene expressionTranscription factorGene expression profilingGeneGene expressionCell biologyComputational biologyGeneticsInternal medicineMedicineEndocrinologyElectrocardiographyHeart rate

Abstract

fetched live from OpenAlex

The cardiac conduction system (CCS) is a network of specialized cardiomyocytes that coordinates electrical impulse generation and propagation for synchronized heart contractions. Although the components of the CCS, including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers, were anatomically discovered more than 100 years ago, their molecular constituents and regulatory mechanisms remain incompletely understood. Here, we demonstrate the transcriptomic landscape of the postnatal mouse CCS at a single-cell resolution with spatial information. Integration of single-cell and spatial transcriptomics uncover region-specific markers and zonation patterns of expression. Network inference shows heterogeneous gene regulatory networks across the CCS. Notably, region-specific gene regulation is recapitulated in vitro using neonatal mouse atrial and ventricular myocytes overexpressing CCS-specific transcription factors, Tbx3 and/or Irx3. This finding is supported by ATAC-seq of different CCS regions, Tbx3 ChIP-seq, and Irx motifs. Overall, this study provides comprehensive molecular profiles of the postnatal CCS and elucidates gene regulatory mechanisms contributing to its heterogeneity. The cardiac conduction system consists of specialized cardiomyocytes that synchronize heart contractions. Here, Oh et al. provide comprehensive molecular profiles of the postnatal cardiac conduction system and elucidate gene regulatory mechanisms contributing to its heterogeneity.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.319
Teacher spread0.298 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations15
Published2024
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicCongenital heart defects researchFrench-language works237,207